This study evaluates the available evidence on pathogenesis and management of LUTS associated with intravesical therapy for Non- Muscle-Invasive-Bladder-Cancer (NMIBC) to formulate a standardized, generalizable therapeutic protocol.

A comprehensive literature review was conducted, analyzing clinical trials, meta-analyses, and clinical guidelines (1992–2025) related to lower urinary tract symptoms (LUTS) in NMIBC patients undergoing intravesical therapy. The review focused on LUTS prevalence, pathophysiology, and pharmacologic and non-pharmacologic interventions, assessing both efficacy and safety.

All three FDA-approved intravesical therapies are associated with varying degrees of LUTS. BCG, the gold standard therapy and  most extensively studied, induces the highest LUTS incidence (50–91%), ranging from acute irritative symptoms to persistent chronic cystitis. Management strategies explored include antibiotics, anti-inflammatories, β₃-agonists, anticholinergics, intravesical hyaluronic acid/chondroitin sulfate, and oral pentosan polysulfate, with variable efficacy (table).
Valrubicin, a chemotherapeutic agent, causes milder LUTS (dysuria in 77%, spasms in 23%) and has fewer treatment discontinuations. Empirical use of phenazopyridine and anticholinergics has been reported, but data on targeted management remain limited.
Nadofaragene firadenovec, a gene therapy, triggers LUTS (bladder spasms in 15%, urgency in 14%), likely due to immune-mediated inflammatory responses. The FDA recommends prophylactic anticholinergics, but optimal dosing and alternative regimens remain unverified.

LUTS management must be tailored to the underlying intravesical agent and severity of symptoms. For BCG-induced LUTS, first-line therapy should include an anti-inflammatory medication e.g. celecoxib (200 mg pre-instillation), preferably with a Beta 3 agonist e.g mirabegron (25 mg/day) for urgency-predominant symptoms. Refractory cases may benefit from intravesical hyaluronic acid/chondroitin sulfate, while a shared decision making should be made regarding anticholinergics (e.g., oxybutynin) due to their conflicting evidence on efficacy and side-effect profile.
Valrubicin-associated LUTS: Given its milder irritative symptoms, phenazopyridine and short-course anticholinergics are empirical choices, though not rigorously evaluated in clinical trials.
Nadofaragene firadenovec-related LUTS: While FDA-endorsed prophylactic oxybutynin, further research is needed to optimize dosing and evaluate alternative strategies (e.g., NSAIDs, Beta 3 agonists, local anesthetic).
Across all therapies, non-pharmacologic adjuncts, such as fluid management prior to instillation, atraumatic catheterization, and heating pads, should be implemented to improve patient comfort and adherence.

A stratified approach to LUTS management, aligned with intravesical agent-specific mechanisms, enhances treatment tolerability and adherence. While BCG management is supported by robust evidence, valrubicin and nadofaragene firadenovec require further clinical trials to validate empirical interventions.